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Interleukin-19 impairment in active Crohn's disease patients
Cantó, E.; Garcia Planella, Esther; Zamora-Atenza, Carlos; Nieto, Juan Camilo; Gordillo, Jordi; Ortiz, Ma. Àngels; Metón Teijeiro, Isidoro; Serrano, Elena; Vegas Lozano, Esteban; García Bosch, O.; Juárez Rubio, Cándido; Vidal i Alcorisa, Sílvia
Universitat de Barcelona
The exact function of interleukin-19 (IL-19) on immune response is poorly understood. In mice, IL-19 up-regulates TNFalpha and IL-6 expression and its deficiency increases susceptibility to DSS-induced colitis. In humans, IL-19 favors a Th2 response and is elevated in several diseases. We here investigate the expression and effects of IL-19 on cells from active Crohn"s disease (CD) patient. Twenty-three active CD patients and 20 healthy controls (HC) were included. mRNA and protein IL-19 levels were analyzed in monocytes. IL-19 effects were determined in vitro on the T cell phenotype and in the production of cytokines by immune cells. We observed that unstimulated and TLR-activated monocytes expressed significantly lower IL-19 mRNA in active CD patients than in HC (logFC =21.97 unstimulated; 21.88 with Pam3CSK4; and 21.91 with FSL-1; p<0.001). These results were confirmed at protein level. Exogenous IL-19 had an anti-inflammatory effect on HC but not on CD patients. IL-19 decreased TNFalpha production in PBMC (850.7675.29 pg/ml vs 2626.06350 pg/ml; p<0.01) and increased CTLA4 expression (22.0461.55% vs 13.9862.05%; p<0.05) and IL-4 production (32.568.9 pg/ml vs 13.562.9 pg/ml; p<0.05) in T cells from HC. IL-10 regulated IL-19 production in both active CD patients and HC. We observed that three of the miRNAs that can modulate IL-19 mRNA expression, were up-regulated in monocytes from active CD patients. These results suggested that IL-19 had an anti-inflammatory role in this study. Defects in IL-19 expression and the lack of response to this cytokine could contribute to inflammatory mechanisms in active CD patients.
Cèl·lules T
Citometria de fluxe
Citoquines
Leucòcits
Malaltia de Crohn
Micro RNAs
Resposta immunitària
RNA
T cells
Flow cytometry
Cytokines
Leucocytes
Crohn's disease
MicroRNAs
Immune response
RNA
cc-by (c) Cantó, Elisabet et al., 2014
http://creativecommons.org/licenses/by/3.0/es
Artículo
info:eu-repo/semantics/publishedVersion
Public Library of Science (PLoS)
         

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